Multi-antibiotic Resistance

Rates of antimicrobial resistance are increasing worldwide. There is increasing evidence that physiological gut microbiota is a large reservoir of antibiotic-resistance genes. Healthy gut microbiota is known to prevent the colonization of the gastrointestinal tract by pathogens, the so-called mechanism of colonization resistance, but this protective mechanism can be altered by therapies that impair gut microbiota, including antibiotics or chemotherapeutics, with consequent colonisation of gut pathogens, including multi-drug resistant bacteria (MDRB). MDRB carriers represent an epidemiological threat to other hospitalized patients and to the whole community, but are also at risk of developing clinical consequences of this colonization, including bloodstream infections from these pathogens. Fecal microbiota transplantation (FMT) has shown high efficacy in the eradication of recurrent C. difficile infection, and initial evidence suggests that this procedure could be useful in eradicating also MDRB, mainly carbapenem-resistant Enterobacteriaceae. However, current evidence is mostly limited to case reports and case series, and to a single randomised trial, which was stopped early and did not draw clear conclusion. In a systematic review of 21 studies and 192 patients, eradication rates ranged from 0% to 100%, and authors concluded that larger, well designed randomised controlled trials are needed to further explore this therapy. The aim of this study is to investigate the efficacy of FMT, compared with placebo FMT, in eradicating gut colonisation from MDRB, focusing on CRE. The investigators will randomize patients colonized by CRE (diagnosed by rectal swab) to FMT from healthy donors or placebo, by colonoscopy. Then, patients will be followed up, rectal swabs will be repeated, and stool samples for culture and microbiome analysis will be collected, up to 3 months after FMT.

Pseudomonas aeruginosa is a pathogenic bacteria for human, especially in hospital settings. It can sometimes be multi-resistant to many or even to all antibiotics usually used for its treatment. The aim of the study is to isolate and produce therapeutic antibodies against the bacteria Pseudomonas aeruginosa in order to provide an alternative treatment to antibiotics in case of infection with an antibiotic-resistant strain of Pseudomonas aeruginosa.

Antibiotic resistance (AR) is a critical public health threat and one of the greatest challenges of the 21st century. In an estimate of 2019, nearly 700.000 infections and 33.000 attributable deaths from multi-drug-resistant bacteria (MDRB) have occurred in Europe in 2015. The gastrointestinal tract is a large reservoir for MDRB, and the gut microbiota can harbor a collection of AR genes, called gut resistome. Preliminary nonrandomized evidence suggests that fecal microbiota transplant (FMT) could be a promising treatment option to eradicate MDRB, but established evidence, as well as mechanisms that underpin this therapeutic pathway, are still unavailable. Leveraging our expertise in FMT (OU1), microbiome (OU2) and MDRB (OU3), we aim to evaluate the efficacy of FMT (from donors with limited presence of AR genes) in eradicating intestinal MDRB through a randomized controlled trial and identifying microbial features that are associated with clinical efficacy and clearance of AR genes